The pilotless drones fired six missiles at Dargah Mandi area, targeting a compound and a vehicle parked inside it.
A security official said that six people were killed in the attack.
The identities of the victims are not known as yet.
A Foreign Office spokesperson said Pakistan condemns the US drone strikes.
"As has been made clear on earlier occasions also, Pakistan regards such strikes as a violation of its sovereignty and territorial integrity.
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The Pakistan Army has launched a ground and air offensive in the area known for having hideouts of the al-Qaeda-linked militants. Armed forces have so far killed more than 200 militants in the operation.
The drone attacks come after the deadly attack at Karachi airport last week that left 39 people dead, including 10 Taliban militants, reportedly Uzbek fighters.
The last drone attack before last week's strikes occurred in Pakistan in December, 2013, killing three insurgents.
The drone strikes had been temporarily halted since then to provide the Pakistani government a chance to hold talks with the Tehrik-e-Taliban Pakistan (TTP) aimed at ending their seven-year insurgency.
Pakistan has criticised drone strikes as a violation of its sovereignty and counter-productive to anti-terror efforts.
After last week's strike, Islamabad had issued a formal condemnation.
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